Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.The idea that when we use a tool we incorporate it into the neural representation of our body (embodiment) has been a major inspiration for philosophy, science, and engineering. While theoretically appealing, there is little direct evidence for tool embodiment at the neural level. Using functional magnetic resonance imaging (fMRI) in male and female human subjects, we investigated whether expert tool users (London litter pickers n = 7) represent their expert tool more like a hand (neural embodiment) or less like a hand (neural differentiation), as compared with a group of tool novices (n = 12).  https://www.selleckchem.com/products/lenalidomide-s1029.html  During fMRI scans, participants viewed first-person videos depicting grasps performed by either a hand, litter picker, or a non-expert grasping tool. Using representational similarity analysis (RSA), differences in the representational structure of hands and tools were measured within occipitotemporal cortex (OTC). Contrary to the neural embodiment theory, we find that the experts group represent their own tool less lindings advance our current understanding for how experience shapes functional organization in high-order visual cortex. Further, this evidence provides an alternative framework to the prominent tool embodiment theory, suggesting instead that experience with tools leads to more distinct, separable hand and tool representations.Neural oscillations play critical roles in information processing, communication between brain areas, learning, and memory. We have recently discovered that familiar visual stimuli can robustly induce 5-Hz oscillations in the primary visual cortex (V1) of awake mice after the visual experience. To gain more mechanistic insight into this phenomenon, we used in vivo patch-clamp recordings to monitor the subthreshold activity of individual neurons during these oscillations. We analyzed the visual tuning properties of V1 neurons in naive and experienced mice to assess the effect of visual experience on the orientation and direction selectivity. Using optogenetic stimulation through the patch pipette in vivo, we measured the synaptic strength of specific intracortical and thalamocortical projections in vivo in the visual cortex before and after the visual experience. We found 5-Hz oscillations in membrane potential (Vm) and firing rates evoked in single neurons in response to the familiar stimulus, consistent withlasticity within V1. Our computational recurrent network model reproduces all these observations and provides a mechanistic framework for studying the role of 5-Hz oscillations in visual familiarity.Alpha-synuclein pathology is associated with dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's patients. Working across human and mouse models, we investigated mechanisms by which the accumulation of soluble α-synuclein oligomers leads to neurodegeneration. Biochemical analysis of the midbrain of α-synuclein overexpressing BAC-transgenic male and female mice revealed age- and region-dependent mitochondrial dysfunction and accumulation of damaged proteins downstream of the RE1 Silencing Transcription Factor (REST). Vulnerable SN dopaminergic neurons displayed low REST levels compared with neighboring protected SN GABAergic neurons, which correlated with the accumulation of α-synuclein oligomers and disrupted mitochondrial morphology. Consistent with a protective role, REST levels were reduced in patient induced pluripotent stem cell-derived dopaminergic neurons carrying the SNCA-Triplication mutation, which accumulated α-synuclein oligomers and mitochondrial damage, and displayed REST targ expression in mice leads to accumulation of α-synuclein oligomers in the absence of overt aggregation, and mitochondrial dysfunction in dopaminergic neurons lacking the RE1 Silencing Transcription Factor. Our findings identify the mechanism of action of RE1 Silencing Transcription Factor and PGC-1α as mediators of dopaminergic vulnerability in α-synuclein BAC-transgenic mice and induced pluripotent stem cell-derived dopaminergic cultures, highlighting their potential as therapeutic targets.The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRNDA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRNDA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRNDA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRNDA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-at neural responses can be altered by head-fixation, which is commonly used in neuroscience.l-3,4-dihydroxyphenylalanine (l-DOPA) is an effective treatment for Parkinson's disease (PD); however, long-term treatment induces l-DOPA-induced dyskinesia (LID). To elucidate its pathophysiology, we developed a mouse model of LID by daily administration of l-DOPA to PD male ICR mice treated with 6-hydroxydopamine (6-OHDA), and recorded the spontaneous and cortically evoked neuronal activity in the external segment of the globus pallidus (GPe) and substantia nigra pars reticulata (SNr), the connecting and output nuclei of the basal ganglia, respectively, in awake conditions. Spontaneous firing rates of GPe neurons were decreased in the dyskinesia-off state (≥24 h after l-DOPA injection) and increased in the dyskinesia-on state (20-100 min after l-DOPA injection while showing dyskinesia), while those of SNr neurons showed no significant changes. GPe and SNr neurons showed bursting activity and low-frequency oscillation in the PD, dyskinesia-off, and dyskinesia-on states. In the GPe, cortically evoked late excitation was increased in the PD and dyskinesia-off states but decreased in the dyskinesia-on state.